Cholesterol-Induced Protein Sorting: An Analysis of Energetic Feasibility

AbstractThe mechanism(s) underlying the sorting of integral membrane proteins between the Golgi complex and the plasma membrane remain uncertain because no specific Golgi retention signal has been found. Moreover one can alter a protein's eventual localization simply by altering the length of its transmembrane domain (TMD). M. S. Bretscher and S. Munro (Science. 261:1280–1281, 1993) therefore proposed a physical sorting mechanism based on the hydrophobic match between the proteins’ TMD and the bilayer thickness, in which cholesterol would regulate protein sorting by increasing the lipid bilayer thickness. In this model, Golgi proteins with short TMDs would be excluded from cholesterol-enriched domains (lipid rafts) that are incorporated into transport vesicles destined for the plasma membrane. Although attractive, this model remains unproven. We therefore evaluated the energetic feasibility of a cholesterol-dependent sorting process using the theory of elastic liquid crystal deformations. We show that the distribution of proteins between cholesterol-enriched and cholesterol-poor bilayer domains can be regulated by cholesterol-induced changes in the bilayer physical properties. Changes in bilayer thickness per se, however, have only a modest effect on sorting; the major effect arises because cholesterol changes also the bilayer material properties, which augments the energetic penalty for incorporating short TMDs into cholesterol-enriched domains. We conclude that cholesterol-induced changes in the bilayer physical properties allow for effective and accurate sorting which will be important generally for protein partitioning between different membrane domains

Lavbundsarealerne ved Fussingø

På engene ved Fussingø Hovedgård blev der i 1997-2001 gennemført en tværfaglig undersøgelse af forskellige græsmarksstrategier, som afgræsning, slæt eller driftsophør, ud fra ønsket om at kunne øge naturkvaliteten under miljøvenlig græsmarksdrift og samtidig forbedre landbrugsproduktionen under sådanne forhold. Med henblik på at få en generel beskrivelse af engarealerne er der indsamlet nøgledata vedrørende geologi, afstrømningsforhold, arealernes driftshistorie, klima, hydrologi og vegetationen på arealerne. Der er benyttet en kombination af ældre beskrivelser og nye registreringer. Engområdet er beliggende i en tunneldal, som stort set følger Skals å forløbet. Der er tørveaflejringer med mindre lag af ler og kalkgytje indlejret lokalt. I den øverste meter af jordlaget er humusindholdet ca. 60%. Der var et højt N-indhold i jorden, men med stor variation indenfor området (1,8-2,7%). Den potentielle netto kvælstof mineralisering var betydeligt højere end det niveau man normalt finder på mineraljord. Afstrømningsoplandet ved Fussingø er på 1948 ha, og det består af fire del-oplande, der afvander til Skals å systemet. Lavbundsarealet på 411 ha udgør 21% af det samlede oplandsareal. Lavbundsarealet består bl.a. af 44% vådområder, som ikke udnyttes landbrugsmæssigt, og af 20% vedvarende græsningsarealer. Engarealerne, som indgik i forsøget, blev i perioden før 1955 og i perioden efter 1987 drevet med græsmarksdrift. I den mellemliggende periode var der mere eller mindre intensiv drift af arealerne med både græsmarksdrift og salgsafgrøder. Klimaet i forsøgsperioden var specielt ved at nedbøren i forårsperioden var stigende gennem de år forsøget varede, og arealerne blev mere og mere fugtige i vækstperioden. Med hensyn til fugtighed var der betydelige forskelle i vandstand fra græsningsfold til græsningsfold. Vegetationen var kulturpræget på østarealet og naturpræget på vestarealet. En forklaring på dette forhold kan være, at der på østarealet var en højere N-mineralisering og et højere indhold af plantetilgængeligt K. Danske lavbundsarealer kan variere meget, og der er ikke grundige beskrivelser af alle lavbundsarealer som af arealerne på Fussingø. Man kan derfor ikke sige, hvor stor en del af de danske lavbundsarealer, der har samme forhold som arealerne, der indgik i undersøgelsen. Ud fra gamle kortoptegnelser er det tidligere vurderet, at en tredjedel af Danmarks lavbundsarealer har humusjord og dermed tilsvarende jordtype som engene ved Fussingø

Upper mantle temperature and the onset of extension and break-up in Afar, Africa

It is debated to what extent mantle plumes play a role in continental rifting and eventual break-up. Afar lies at the northern end of the largest and most active present-day continental rift, where the East African Rift forms a triple junction with the Red Sea and Gulf of Aden rifts. It has a history of plume activity yet recent studies have reached conflicting conclusions on whether a plume still contributes to current Afar tectonics. A geochemical study concluded that Afar is a mature hot rift with 80 km thick lithosphere, while seismic data have been interpreted to reflect the structure of a young, oceanic rift basin above mantle of normal temperature. We develop a self-consistent forward model of mantle flow that incorporates melt generation and retention to test whether predictions of melt chemistry, melt volume and lithosphere–asthenosphere seismic structure can be reconciled with observations. The rare- earth element composition of mafic samples at the Erta Ale, Dabbahu and Asal magmatic segments can be used as both a thermometer and chronometer of the rifting process. Low seismic velocities require a lithosphere thinned to 50 km or less. A strong positive impedance contrast at 50 to 70 km below the rift seems linked to the melt zone, but is not reproduced by isotropic seismic velocity alone. Combined, the simplest interpretation is that mantle temperature below Afar is still elevated at 1450◦C, rifting started around 22–23 Ma, and the lithosphere has thinned from 100 to 50 km to allow significant decompressional melting

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

The interrelation between temperature regimes and fish size in juvenile Atlantic cod (Gadus morhua): effects on growth and feed conversion efficiency

The present paper describes the growth properties of juvenile Atlantic cod (Gadus morhua) reared at 7, 10, 13 and 16 °C, and a group reared under “temperature steps” i.e. with temperature reduced successively from 16 to 13 and 10 °C. Growth rate and feed conversion efficiency of juvenile Atlantic cod were significantly influenced by the interaction of temperature and fish size. Overall growth was highest in the 13 °C and the T-step groups but for different reasons, as the fish at 13 °C had 10% higher overall feeding intake compared to the T-step group, whereas the T-step had 8% higher feeding efficiency. After termination of the laboratory study the fish were reared in sea pens at ambient conditions for 17 months. The groups performed differently when reared at ambient conditions in the sea as the T-step group was 11.6, 11.5, 5.3 and 7.5% larger than 7, 10, 13 and 16 °C, respectively in June 2005. Optimal temperature for growth and feed conversion efficiency decreased with size, indicating an ontogenetic reduction in optimum temperature for growth with increasing size. The results suggest an optimum temperature for growth of juvenile Atlantic cod in the size range 5–50 g dropping from 14.7 °C for 5–10 g juvenile to 12.4 °C for 40–50 g juvenile. Moreover, a broader parabolic regression curve between growth, feed conversion efficiency and temperature as size increases, indicate increased temperature tolerance with size. The study confirms that juvenile cod exhibits ontogenetic variation in temperature optimum, which might partly explain different spatial distribution of juvenile and adult cod in ocean waters. Our study also indicates a physiological mechanism that might be linked to cod migrations as cod may maximize their feeding efficiency by active thermoregulation

A multi-center study on the attitudes of Malaysian emergency health care staff towards allowing family presence during resuscitation of adult patients

BACKGROUND The practice of allowing family members to witness on-going active resuscitation has been gaining ground in many developed countries since it was first introduced in the early 1990s. In many Asian countries, the acceptability of this practice has not been well studied. AIM We conducted a multi-center questionnaire study to determine the attitudes of health care professionals in Malaysia towards family presence to witness ongoing medical procedures during resuscitation. METHODS Using a bilingual questionnaire (in Malay and English language), we asked our respondents about their attitudes towards allowing family presence (FP) as well as their actual experience of requests from families to be allowed to witness resuscitations. Multiple logistic regression was used to analyze the association between the many variables and a positive attitude towards FP. RESULTS Out of 300 health care professionals who received forms, 270 responded (a 90% response rate). Generally only 15.8% of our respondents agreed to allow relatives to witness resuscitations, although more than twice the number (38.5%) agreed that relatives do have a right to be around during resuscitation. Health care providers are significantly more likely to allow FP if the procedures are perceived as likely to be successful (e.g., intravenous cannulation and blood taking as compared to chest tube insertion). Doctors were more than twice as likely as paramedics to agree to FP (p-value = 0.002). This is probably due to the Malaysian work culture in our health care systems in which paramedics usually adopt a 'follow-the-leader' attitude in their daily practice. CONCLUSION The concept of allowing FP is not well accepted among our Malaysian health care providers

Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of beta-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gscoupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.Diabetes mellitus: pathophysiological changes and therap

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented